Medicine Professional Corporation, Cambridge, Ontario, Canada.
Diabetes Obes Metab. 2010 Dec;12(12):1058-65. doi: 10.1111/j.1463-1326.2010.01251.x.
To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo.
A 26-week, multi-country (Canada, Mexico, Romania, South Africa and the USA), randomized, double-blind, placebo-controlled study compared exenatide twice-daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA(1c) 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2-week, single-blind, lead-in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA(1c) change at endpoint (Week 26 or last-observation-carried-forward).
Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA(1c) significantly more than placebo [-0.84% (s.e. 0.20) vs. -0.10% (0.23), treatment difference -0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, -1.4 (s.e. 0.6) kg vs. placebo, -0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA(1c) and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups.
Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA(1c) without associated hypoglycaemia.
检验在噻唑烷二酮（TZDs）加或不加二甲双胍的基础上加用艾塞那肽可改善血糖控制的假说，优于安慰剂。
在加拿大、墨西哥、罗马尼亚、南非和美国进行的一项 26 周、多国、随机、双盲、安慰剂对照研究中，将艾塞那肽每日 2 次与安慰剂在 165 例血糖控制欠佳（HbA1c8.2%[标准差 0.9]，空腹血清葡萄糖 9.1[2.6]mmol/l，体重 93.9[17.8]kg，糖尿病病程 6.4[4.3]年）、加用或不加用二甲双胍的 TZDs 治疗的患者中进行比较。在 2 周的单盲导入期后，患者按照 2:1 的比例随机接受艾塞那肽或安慰剂加用当前治疗方案。主要终点为治疗终点（第 26 周或最后观察到的向前结转）时的 HbA1c 变化。
仅 8 例患者接受了单纯 TZD 治疗。艾塞那肽显著降低 HbA1c 水平，优于安慰剂组（-0.84%[0.20]比-0.10%[0.23]，治疗差异-0.74%[0.16]，p<0.001）。在治疗终点时，两种治疗方法的体重减轻程度相似[艾塞那肽，-1.4[0.6]kg 比安慰剂组，-0.8[0.7]kg，p=0.176]。与安慰剂相比，近 71%的患者用艾塞那肽治疗后 HbA1c 和体重均降低，而安慰剂组仅为 54%。最常见的不良事件（艾塞那肽与安慰剂）为恶心（12%比 2%，p=0.037）、呕吐（8%比 0%，p=0.031）和头痛（4%比 4%）。分别有 4%和 2%的艾塞那肽和安慰剂治疗患者出现确诊（血糖<3.0mmol/l）的轻度低血糖。两组低血糖发生率无显著差异。
艾塞那肽加用 TZDs 单独或与二甲双胍联合应用可显著改善血糖控制，HbA1c 显著改善而无相关低血糖。
